Differential Inhibition of Thrombin Activity and Thrombin Generation by a Synthetic Direct Thrombin Inhibitor (Napsagatran, Ro 46-6240) and Unfractionated Heparin in Patients with Deep Vein Thrombosis

Autor:	Rapold Hj, Hulting J, Ehringer H, Rasche H, Henri Bounameaux, Reber G, Gast A, Tschopp Tb
Rok vydání:	1999
Předmět:	biology business.industry medicine.drug_class Anticoagulant Hematology Heparin Pharmacology Thrombin Coagulation Enzyme inhibitor Direct thrombin inhibitor Antithrombotic Immunology medicine biology.protein business medicine.drug Discovery and development of direct thrombin inhibitors
Zdroj:	Thrombosis and Haemostasis. 81:498-501
ISSN:	2567-689X 0340-6245
DOI:	10.1055/s-0037-1614512
Popis:	Summary Background: Direct thrombin inhibitors belong to a new class of antithrombotic drugs whose effects on blood coagulation in vivo in patients suffering from acute thrombotic conditions have not yet been fully explored. Methods and Results: One hundred and five patients with acute proximal deep-vein thrombosis were randomized to receive a continuous intravenous infusion of napsagatran, a novel synthetic thrombin inhibitor, at a fixed dose of 5 mg/h (n = 36) or 9 mg/h (n = 25) for five days, or APTT-adjusted unfractionated heparin (UFH, n = 44) for the same time. In these patients, thrombin activity and thrombin generation could be assessed by measuring thrombin-antithrombin III complexes (TAT) and prothrombin fragment 1+2 (F1+2), respectively, on three occasions. At baseline, TAT and F1+2 did not differ among the three groups. On Day 2 (steady state), TAT significantly decreased in all groups, and the decrease was significantly more pronounced in the patients given higher-dose napsagatran. F1+2 decreased significantly only in UFH-treated patients. Two hours after cessation of the infusion, the TAT levels increased in the two napsagatran groups but not in the UFH group, whilst F1+2 went back to the baseline levels in the napsagatran-treated patients but remained low in the UFH-treated patients. There was no rebound effect. Conclusions: The data presented suggest that direct thrombin inhibition with napsagatran at 9 mg/h is more potent than UFH in attenuating thrombin activity, but is less potent than UFH in inhibiting thrombin generation. The real significance of these findings will have to be substantiated in further trials with clinically relevant endpoints.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::29c09897e758f062ab944b8ebdb18a50 https://doi.org/10.1055/s-0037-1614512 Zobrazit plný text záznamu